Is NEBL p.Ser482Arg (c.1444A>C) pathogenic?

NEBL p.Ser482Arg (c.1444A>C) is classified Uncertain significance in NEBL (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: likely pathogenic (0.8583); Absent from gnomAD v4.1; Associated with NEBL-related Cardiomyopathy.

What condition is associated with NEBL p.Ser482Arg (c.1444A>C)?

NEBL p.Ser482Arg (c.1444A>C) is associated with NEBL-related Cardiomyopathy (ClinVar).

How common is NEBL p.Ser482Arg (c.1444A>C) in the general population?

NEBL p.Ser482Arg (c.1444A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NEBL p.Ser482Arg (c.1444A>C)?

AlphaMissense predicts likely pathogenic (score 0.8583) — an in-silico prediction, not a clinical call.

NEBL p.Ser482Arg

c.1444A>C · rs2491827078 · VCV2584565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8583 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

NEBL-related Cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.8583	likely pathogenic · top 6% in NEBL
REVEL	0.379	indeterminate
SaProt	LLR -9.29	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.3	GERP 0.68, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 111 kb · p 7.4e-07 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NEBL
Protein: p.Ser482Arg
Coding: c.1444A>C
MANE Select: NM_006393
dbSNP: rs2491827078
Type: single nucleotide variant
Location: chr10:20835518 (GRCh38)
Gene constraint: LOEUF 1.036 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 62.00 · 1 PDB

Full NEBL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NEBL-related Cardiomyopathy

Similar variants

NEBL p.Tyr959Cys Uncertain significance ★ ⚠ same condition
NEBL p.Gly724Glu Uncertain significance ⚠ same condition
NEBL p.Phe852= Likely benign same condition
NEBL p.Phe98= Likely benign same condition
NEBL p.Asp390_Leu391insTer Uncertain significance same condition
NEBL c.259-9_259-8dup Likely benign same condition
NEBL c.1227+5G>A Uncertain significance ★★ same type
NEBL c.1870-1G>A Uncertain significance ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/nebl-p-ser482arg (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown